Section of Behavioural Neurosciences, Department of Cell Biology and Neurosciences, Istituto Superiore di Sanità, Viale Regina Elena 299, 00161 Rome, Italy.
Psychoneuroendocrinology. 2011 Apr;36(3):339-51. doi: 10.1016/j.psyneuen.2010.08.011. Epub 2010 Sep 26.
Major depression is a chronic, recurring and potentially life-threatening illness that affects up to 10% of the population worldwide. Pharmacological and genetic studies highlight the serotonergic system as being a key player in the disorder. However, despite drugs designed to boost serotonin transmission represent the first line of therapy for depression, the role of this system still remains elusive. Here, I propose a new theoretical framework, the undirected susceptibility to change model, potentially accounting for the experimental and clinical results concerning the role of this neurotransmitter in depression. Since the capacity of the individual to change its physiology and behavior according to the environment is dependent on neural plasticity which, in turn, is controlled by serotonin, I assume that changes in the levels of serotonin affect the sensitivity to the environment. Consequently, the undirected susceptibility to change model predicts that an increase of serotonin levels, for instance induced through selective serotonin reuptake inhibitor (SSRI) administration, does not affect mood per se, but--acting as a catalyzer--enhances neural plasticity and, thus, the effects of the environment on mood. However, since the environment can be either supportive or adverse, its effects can be beneficial or detrimental. Therefore enhancing the serotonin system can increase the likelihood both of developing the psychopathology and recovering from it. This model, on the one hand, suggests an explanation for the limited SSRI efficacy described in clinical studies and allows apparently contradictory data to be reconciled; on the other, it describes neural plasticity as a double edged sword that, according to the quality of the environment, may have either positive or negative consequences.
重度抑郁症是一种慢性、复发性且可能危及生命的疾病，全球有高达 10%的人口受其影响。药理学和遗传学研究强调，血清素能系统是这种疾病的关键因素。然而，尽管旨在增强血清素传递的药物是治疗抑郁症的一线药物，但该系统的作用仍然难以捉摸。在这里，我提出了一个新的理论框架，即无方向易变模型，该模型可能解释了关于这种神经递质在抑郁症中的作用的实验和临床结果。由于个体根据环境改变其生理和行为的能力取决于神经可塑性，而神经可塑性又受血清素控制，因此我假设血清素水平的变化会影响对环境的敏感性。因此，无方向易变模型预测，血清素水平的增加，例如通过选择性血清素再摄取抑制剂（SSRI）的给药来实现，本身并不会影响情绪，而是——作为催化剂——增强神经可塑性，从而增强环境对情绪的影响。然而，由于环境既可以是支持性的，也可以是不利的，因此其影响既可以是有益的，也可以是有害的。因此，增强血清素系统可以增加出现精神病理学和从中恢复的可能性。该模型一方面为临床研究中描述的 SSRI 疗效有限提供了解释，并使看似矛盾的数据得到协调；另一方面，它将神经可塑性描述为一把双刃剑，根据环境的质量，它可能产生积极或消极的后果。
